Eye Movement Abnormalities in Multiple Sclerosis: Pathogenesis, Modeling, and Treatment

Abstract

Multiple sclerosis (MS) commonly causes eye movement abnormalities that may have a significant impact on patients’ disability. Inflammatory demyelinating lesions, especially occurring in the posterior fossa, result in a wide range of disorders, spanning from acquired pendular nystagmus (APN) to internuclear ophthalmoplegia (INO), among the most common. As the control of eye movements is well understood in terms of anatomical substrate and underlying physiological network, studying ocular motor abnormalities in MS provides a unique opportunity to gain insights into mechanisms of disease. Quantitative measurement and modeling of eye movement disorders, such as INO, may lead to a better understanding of common symptoms encountered in MS, such as Uhthoff’s phenomenon and fatigue. In turn, the pathophysiology of a range of eye movement abnormalities, such as APN, has been clarified based on correlation of experimental model with lesion localization by neuroimaging in MS. Eye movement disorders have the potential of being utilized as structural and functional biomarkers of early cognitive deficit, and possibly help in assessing disease status and progression, and to serve as platform and functional outcome to test novel therapeutic agents for MS. Knowledge of neuropharmacology applied to eye movement dysfunction has guided testing and use of a number of pharmacological agents to treat some eye movement disorders found in MS, such as APN and other forms of central nystagmus.

Eye movement evaluation in Multiple Sclerosis and Parkinson’s Disease using a Standardized Oculomotor and Neuro-ophthalmic Disorder Assessment (SONDA)

“…In MS, inflammatory demyelinating lesions in different brain areas result in a wide range of oculomotor disorders: most commonly, static and dynamic ocular misalignment (Serra et al, 2018) coupled with dysmetric saccadic behavior (Serra et al, 2003). Furthermore, fixation (Mallery et al, 2018), smooth pursuit (Lizak et al, 2016), and vestibulo-ocular responses (Huygen et al, 1986) are also often impaired.…”

Peer Review #1 of "Relationships between neuropsychological and antisaccade measures in multiple sclerosis patients (v0.1)"

“…Although, we must acknowledge that we found the results reported in the literature, from different laboratories and acquired with different equipment, remarkably consistent. For a good review of the clinical utility of AS task and other eye movements metrics in MS we recommend a recent review by Serra (Serra et al 2018 Manuscript to be reviewed associated with other cognitive measures such as processing speed (measured with the SDMT) and verbal fluency/executive function (measure with COWAT) (Whiteside et al 2016). These findings suggest that the Stroop performance can be influenced by unspecific cognitive deficits (Denney & Lynch 2009).…”

“…Exclusion criteria were: ongoing relapse/relapse in the previous month, presence of clinically diagnosed cognitive impairment, history of traumatic brain injury and/or stroke, depression (self-reported or detected during the study using the Beck Depression Inventory (Beck et al 1988)). Those with clinically visible oculomotor abnormalities were not recruited (e.g., nystagmus or internuclear ophthalmoplegia, see references (Frohman et al 2005;Serra et al 2018 (Table 1); Serra et al 2003) for comprehensive lists. Controls were subject to equivalent exclusion criteria.…”

Relationships between neuropsychological and antisaccade measures in multiple sclerosis patients

“…Those with clinically visible oculomotor abnormalities were not recruited (e.g. nystagmus or internuclear ophthalmoplegia, see references ( Frohman et al, 2005 ; Serra, Chisari & Matta, 2018 ( Table 1 ); Serra et al, 2003 ) for comprehensive lists. Controls were subject to equivalent exclusion criteria.…”